The goal os this program project is to combine appropriate working teams immunologists, molecular geneticists, microbiologists and clinicians to study the molecular immunology of sexually transmitted diseases caused by Chlamydia trachomatis. The decision to work on a single important STD pathogen was deliberate effort to blend talents from a variety of disciplines in such a way to make it possible to comprehensively evaluate the overall immune response to C. trachomatis, especially in the context of progress from uncomplicated lower genital tract infections to sequelae of chronic upper genital tract disease, including involuntary infertility and adverse outcomes of pregnancy in women. Studies are proposed to evaluate, at the molecular level the requirements for processing and presentation of chlamydial antigens, and identification of relevant T cell epitopes (project 1, DeMars) and the nature and function of antigen presenting cells in vivo at the site of upper genital tract disease (project 2, Arno and Bick). Work also is proposed to define the process of chlamydial persistence in human polarized epithelial cells, including primary endometrial cells; how immune reactivity contributes to this process and the molecular characterization of chlamydia as they exist in the persistent state (project 3, Byrne). Finally, work is proposed to determine if protective immunity occurs in individuals who recover from lower genital tract disease; and if so define the requirements based on epitopic specificity of antibody responses that result in protection (project 4, Batteiger). These projects will be served by an administrative core in Madison (Byrne), a clinical core in Indianapolis (Jones) and a peptide synthesis core in Madison (Niece). The overall aim of comprehensively increasing our understanding of immunity to chlamydial genital tract disease will be accomplished by closely networking each of the four research projects with each other, with the core facilities and with collaborators who are directly involved in complementary research programs via STD Center grants. It is anticipated that this focused, comprehensive approach will serve to increase our knowledge in this field in a way that has been difficult because of the lack of coordination of work done in this area. This program project will reduce fragmentation of effort and facilitate a multicenter cooperative effort with clear goals in mind.